My long term career goal is to use molecular and cellular biology tools to investigate cell differentiation and growth control in an animal virus model of oncogenesis. My immediate career goal is to determine the mechanisms involved in, and develop clinical interventions for, human hepatitis B virus associated hepatic oncogenesis. Throughout my career, I have been very fortunate to be able to work with many outstanding scientists at MIT, Harvard, Penn and UTMB- Galveston. Part of the reason that I chose to come to UTMB- Galveston is the favorable intellectual climate in the Houston- Galveston area. The convenient interactions among MD Anderson Hospital, Baylor college, Rice University, University of Houston, UTMB-Galveston and their affiliated hospitals have been very appealing to many young scientists. I have found UTMB-Galveston to be a very pleasant and stimulating place which will enable me to interact with many friendly and resourceful colleagues such as Drs. David Walker, Aubrey Thompson, Brad Thompson, Samuel Wilson, Miles Cloyd, Samuel Baron, John Papaconstantinou. Although this environment is a good niche for a young scientist to establish an independent career, this factor alone may not be sufficient. Over the past few years at Penn, I have often been sidetracked by numerous non-research obligations and the ordeal of learning grantsmanship. Once an RCDA is awarded, our Department Chairman at UTMB assures me he will reduce my teaching and administrative responsibilities to a minimum. Chronic infection with human hepatitis B virus (HBV) is a major cause of liver cancer. Most recently, one HBV variant with a hotspot mutation within the precore sequences of HBV has been identified from the sera of a significant subset of chronic hepatitis patients. A simple escape from immunosurveillance cannot explain the high frequency occurrence of mutations at these hotspots. A number of hypotheses concerning the potential selective advantage of these precore variants over the wild type virus will be tested in a tissue culture system.